Glycosylation is a process by which sugars are attached to proteins, and largely divided into N-glycosylation and O-glycosylation. Glycosylation is catalyzed by glycosyltransferase, and about 200 kinds of glycosyltransferases have been reported. The kind and structure of sugars may influence protein folding, stability, solubility, and sensitivity to protease, serum half-life, antigenicity, increase of activity, etc.
DKK2, a repressor protein of Wnt, belongs to the Dickkopf family, and has been reported to act as an inhibiting factor or stimulating factor of Wnt signaling pathways (Wu W et al., Curr. Biol., 10(24), pp. 1611-1614, 2000). DKK2 may contain into two specific cysteine-rich domains (CRD) and includes various lengths of connection regions. Particularly, DKK2 highly conserves a cystein-2 region among the Dickkopf family members which has 10 cysteine amino acids (Krupnik V E et al., Gene, 238(2), pp. 301-313, 1999). DKK2 is a protein that is hard to produce with low expression efficiency in animal cells, and thus development of therapeutic agents using DKK2 is being delayed.
Accordingly, there is a demand for DKK2 which maintains a binding affinity or has an improved binding affinity for its substrate and also shows increased expression efficiency.